MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial (NCT01411345), a randomized na study. The primary outcome is PSA Response Rate.

2. Clinical Question

The trial’s stated hypothesis was that increasing radiation dose to a functional MRI-defined lesion in the prostate bed would improve the initial complete response, defined in the record as reduction in PSA to less than 0.1 ng/mL. The primary outcome therefore focuses on a biochemical measure at a specified follow-up point, rather than directly reporting all aspects of disease control or quality of life.

The record also lists questions about biomarker expression in enhancing and non-enhancing tumor regions, circulating DNA and tumor cells, anxiety related to prostate cancer, toxicity, quality of life, failure-free survival, and overall survival. These are additional aims or outcomes, not the primary question addressed by the posted PSA response figures. Results for those outcomes are not reported in the registry record.

3. Trial Design

The MAPS record describes a randomized, parallel-arm trial of salvage radiotherapy after prostatectomy. Masking is listed as none, and enrollment is 37. The record’s phase field is listed as NA, while the official title calls the study a Phase II randomized trial and the arm descriptions use Phase 2 and Phase 3 labels. The record does not explain those differing labels.

The two interventions are Standard Salvage Radiation Treatment (SSRT) and Mapped Tumor Salvage RT (MTSRT). For SSRT, the arm description specifies 68 Gy in 34 treatment sessions to the clinical target volume. It also says 51 Gy in 34 sessions can be given to the pelvic nodes, and identifies this arm as closed.

The MTSRT descriptions specify the same 68 Gy in 34 sessions to the clinical target volume, with functional imaging used to define the gross tumor volume. That volume receives 2.25 Gy per day for a total of 76.5 Gy. The record describes this as biologically equivalent to 80 Gy in 2.0 Gy sessions, assuming an α/β ratio of 3. A Phase 2 MTSRT description and a Phase 3 MTSRT description are both present; the latter says the arm “was conti,” and the available wording does not clarify the truncated text.

The primary outcome is the percentage of participants with PSA less than 0.1 ng/mL at 21 months after completion of study treatment. The primary-outcome timeframe is listed as up to 23 months. The record reports 15 participants in the SSRT outcome group and 20 in the MTSRT outcome group. It lists University of Miami as sponsor, a start date of 2012-07-12, a primary completion date of 2024-02-13, and a status of active, not recruiting. The allocation procedure and the original statistical design details are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Participants that completed a PSA evaluation at 21 months after completion of study treatment.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as PSA Response Rate, measured over Up to 23 months.

The primary endpoint is the PSA response rate: the percentage of study participants with PSA less than 0.1 ng/mL at 21 months after completing study treatment. The analysis population is specified as participants who completed a PSA evaluation at that time. The registry gives the outcome timeframe as up to 23 months.

PSA is a biochemical measure, and the registry’s hypothesis treats reduction below the stated threshold as an initial complete response. Reporting a percentage makes the endpoint interpretable as the proportion of evaluated participants who met that threshold in each arm. The endpoint is measured at a defined follow-up point, so it describes response at that time rather than the full course of subsequent disease control.

The outcome is binary at the participant level: each person either meets the PSA threshold or does not. The response rate is therefore a proportion, and its uncertainty depends in part on how many participants had an evaluable PSA assessment. The record does not report the individual PSA measurements, the handling of assessments outside the stated follow-up point, or whether participants without an assessment were included in any other way.

The primary endpoint is distinct from the listed secondary outcomes, which include treatment-emergent toxicity, health-related quality of life, biochemical and clinical failure, failure-free survival, overall survival, and tissue biomarker expression. Their results are not reported in the registry record.

7. Results Posted in the Registry

• Arm II: Mapped Tumor Salvage RT (MTSRT): 85.0% (17/20) versus 66.7% (10/15) on control; risk difference 18.3 percentage points (95% CI -10.2 to 46.9), risk ratio 1.28 (0.85–1.91); unadjusted two-proportion z-test p = 0.201.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary response summarized as a percentage. Each evaluated participant is classified according to whether PSA was less than 0.1 ng/mL at 21 months after study treatment. The arm-specific percentages describe the observed proportion meeting that definition. Because the endpoint is a proportion, its precision depends on the number of participants contributing an assessment as well as the observed response rate.

What does the risk difference describe?

The risk difference compares the response proportions by subtraction, expressed on the probability scale. The posted estimate is 0.183 for MTSRT compared with SSRT. A positive estimate means the observed proportion was higher in the MTSRT group; it does not by itself establish that the underlying group probabilities differ. The confidence interval communicates uncertainty around that estimate and ranges from -0.102 to 0.469.

How should the relative measures be read?

The risk ratio compares the response probabilities as a ratio, while the odds ratio compares the odds of response. The registry reports a risk ratio of 1.275 and an odds ratio of 2.833. These use different scales, so their numerical values are not interchangeable. For ratios, a value of 1 represents no relative difference. The reported intervals are broad and include 1: 0.853 to 1.907 for the risk ratio, and 0.555 to 14.47 for the odds ratio.

What does the p-value contribute?

The posted unadjusted p-value is 0.201. In general, a p-value describes how unusual data at least as discrepant as those observed would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry does not report the test used or a fuller statistical analysis plan, so the p-value should be read as the unadjusted comparison reported in the record.

Why do confidence intervals matter?

In general, a confidence interval gives a range of estimates compatible with the data and the method used to construct it. It makes the uncertainty in the point estimate visible. For this endpoint, the risk-difference interval includes zero; the relative-effect intervals include 1. Those features mean the posted results do not rule out no arm difference on the corresponding scales. The intervals also span effects in both directions, so the data are not very precise about the magnitude of any difference.

Why can proportions be uncertain in small groups?

General statistical reasoning applies: estimates based on limited numbers of observations can vary substantially from sample to sample. A few participants changing response category can materially affect an arm percentage when the group is small. The response groups contain 15 participants for SSRT and 20 for MTSRT, so the percentages should be interpreted alongside their confidence interval rather than as exact population values. The registry does not report a model-based adjustment for other characteristics.

What does over-dispersion mean in general?

For outcomes modeled as counts or proportions, over-dispersion means the observed variability is greater than the model expects. If it is present and ignored, standard errors can be too small and intervals too narrow. The primary endpoint is reported as a binary percentage, but the registry does not report a model or diagnostic assessment for over-dispersion. No conclusion about its presence can be drawn from the posted results.

The comparison is presented as unadjusted. Whether the trial used other prespecified models, adjustment variables, sensitivity analyses, or interim analyses is not reported in the registry record. The registry also lists 10 outcome measures, 9 secondary outcomes, and 0 analyses. The record does not explain how the outcomes relate to the analyses count. As a result, the posted primary comparison is not enough to reconstruct a complete analysis plan or determine how other analyses were conducted.

10. Confidence Intervals and Precision

The point estimate for the risk difference is 0.183, but the confidence interval runs from -0.102 to 0.469. Because the interval crosses zero, the posted data are compatible with no difference and with a difference in either direction. Its width signals that the estimate is not precise enough to pin down the size of an underlying difference.

The relative measures also show substantial uncertainty. The risk ratio is 1.275, with a confidence interval from 0.853 to 1.907. The odds ratio is 2.833, with a confidence interval from 0.555 to 14.47. Each interval includes 1, the no-relative-difference value. The estimates therefore do not identify a narrow range of plausible relative effects.

In general, a confidence interval reflects both the observed data and the statistical method used to calculate it. It is not a guarantee that the true value lies within the interval, nor does it indicate that all values inside it are equally likely. The registry does not report the interval-construction method. The posted group sizes—15 for SSRT and 20 for MTSRT—are modest, which limits the amount of information available for estimating response rates precisely.

The intervals should be read together with the point estimates and the unadjusted p-value of 0.201. A lack of precision is not proof that the arms are identical; it means the posted results leave considerable uncertainty about the size and direction of a difference.

11. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the trial’s original design justification. They assume a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. For this binary outcome, the figures are participants per arm, not total events.

Using 100% of the observed effect, the illustration gives 85 participants per arm for 80% power and 113 participants per arm for 90% power. Using 75% of the observed effect, it gives 161 participants per arm for 80% power and 215 participants per arm for 90% power. Using 50% of the observed effect, it gives 382 participants per arm for 80% power and 511 participants per arm for 90% power.

In general, power is the chance that a planned study will detect an effect of a specified size under the chosen assumptions if that effect is present. The 80% and 90% columns represent different planning targets: the latter aims for a greater chance of detection under the same assumptions, and therefore requires more participants. Smaller effects are harder to distinguish from random variation, so planning to detect a smaller fraction of the observed effect requires more participants per arm.

These are planning illustrations, not observed power. They do not show the probability that the posted result is correct or the probability that the treatment effect exists. The trial’s own sample-size justification and original design assumptions are not reported in the registry record. The illustration should therefore not be mistaken for the trial’s actual planned enrollment target or for evidence that the trial had a particular level of power.

12. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.667; treatment proportion p₁ = 0.850; average p̄ = 0.758.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6054 = 1.1866.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5914 = 0.4977.
4. n = (1.1866 + 0.4977)² / (0.1833)² = 84.4, rounded up to 85 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.666666666666667                          # control proportion
p1 <- 0.85                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1411345)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 85 (80% power), 113 (90% power)
 75% of observed effect: n per arm = 161 (80% power), 215 (90% power)
 50% of observed effect: n per arm = 382 (80% power), 511 (90% power)
power.prop.test: 84.4 
Simulated power at n = 85 per arm: 0.815 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures, including the primary PSA response rate and secondary outcomes covering toxicity, quality of life, failure, survival, and tissue biomarkers. It reports 9 secondary outcomes and 0 analyses. The relationship between those registry counts is not explained. No multiplicity strategy—such as a prespecified hierarchy or adjustment for multiple comparisons—is reported in the registry record.

Multiplicity matters in general because examining many outcomes can increase the chance of observing a nominally unusual result even when there is no underlying effect. The posted primary comparison is unadjusted, and the registry does not state whether other outcomes were tested, how they were prioritized, or whether any correction was planned. The listed secondary outcomes should not be treated as statistically confirmed findings when their results and analysis details are not reported.

The primary analysis population is defined as participants who completed a PSA evaluation at 21 months after treatment. The result groups contain 15 participants in SSRT and 20 in MTSRT. The record does not explain whether anyone assigned to either arm lacked an endpoint assessment, how such missing assessments were handled, or whether any sensitivity analysis was performed. It also does not state whether the analysis followed an intention-to-treat principle or another analysis-population definition.

The safety denominators differ from the primary endpoint denominators for MTSRT: safety figures use 22 participants, while the endpoint group uses 20. The record does not explain the difference. For SSRT, the record lists 15 participants in both contexts. There is not enough information to infer why denominators differ or what effect, if any, that difference has on the estimates.

The registry does not report baseline comparability, details of randomization, an analysis plan, adjustment variables, interim analyses, or procedures for handling missing data. These omissions prevent a fuller assessment of outcome selection, analysis populations, and potential sources of bias from the registry record alone.

14. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac disorders, other (4.5%), hematuria (4.5%), sick sinus syndrome (4.5%), ventricular tachycardia (4.5%).

The registry lists serious adverse events for 15 participants at risk in SSRT and 22 in MTSRT. It reports 0 serious events in the SSRT group and 4 in the MTSRT group. The record lists Cardiac Disorders, Other; Hematuria; Sick Sinus Syndrome; and Ventricular tachycardia among the top serious terms, each at 4.5%.

It also reports other adverse-event figures for 15 participants at risk in SSRT, with 15 affected, and 22 at risk in MTSRT, with 21 affected. One death is listed in SSRT and 0 in MTSRT. The registry does not say whether the death was related to treatment or provide further details about its cause.

These figures describe the safety entries posted in the record; they do not establish causation. The serious-event counts are not the same as the number of distinct event terms, and the listed terms do not provide a full account of event timing, severity, duration, or attribution. The record does not report comparative statistical tests for safety outcomes. The differing MTSRT safety and endpoint denominators also mean that the safety counts should not be substituted for the PSA response analysis groups.

15. What the Result Does, and Does Not, Mean

The posted results show PSA response rates of 66.6% for SSRT and 85.0% for MTSRT among the participants included in each reported endpoint group. The risk-difference estimate is 0.183 in the direction of a higher observed response percentage in MTSRT. However, its confidence interval extends from -0.102 to 0.469, and the unadjusted p-value is 0.201. The interval includes no difference and values on either side of it, so the results do not precisely establish the size or direction of an underlying difference.

This endpoint has a specific scope: it measures PSA below 0.1 ng/mL at 21 months after completion of study treatment among participants with an assessment at that time. It does not, by itself, summarize longer-term outcomes or all aspects of the treatment experience. The registry lists other outcomes, but their results are not reported in the registry record.

The findings do not establish that either treatment is superior, nor do they prove that the treatments have identical effects. The uncertainty is substantial, and the registry does not provide enough analysis detail to assess every aspect of the comparison. In particular, the record does not explain missing PSA assessments, the difference in MTSRT endpoint and safety denominators, or the statistical methods beyond the unadjusted comparison.

In general, a randomized design can support comparison between groups, but interpretation also depends on how assignment was carried out, follow-up was managed, and outcomes were analyzed. Those details are not reported in the registry record. The posted percentages should therefore be read as descriptive estimates from the recorded outcome groups, not as a basis for individual treatment decisions or a conclusion about clinical benefit.

16. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a percentage-based endpoint can look favorable in one arm while still leaving considerable uncertainty about the comparative effect. The observed response percentages are 66.6% for SSRT and 85.0% for MTSRT, but the confidence interval for the risk difference includes zero and spans a broad range. Reporting only the two percentages would hide much of that uncertainty.

The comparison also illustrates why the endpoint denominator matters. PSA response is defined among participants who completed an assessment at 21 months, and the reported groups contain 15 and 20 participants. The MTSRT safety group contains 22 participants, with no registry explanation for the different denominator. Keeping the populations distinct is essential when interpreting efficacy and safety figures.

The record makes several additional outcomes visible, including toxicity, quality of life, failure-free survival, overall survival, and biomarkers. But outcomes listed without corresponding results or analysis details cannot be used to resolve uncertainty in the primary endpoint. The registry lists 10 outcome measures, 9 secondary outcomes, and 0 analyses, while not explaining the relationship among those entries.

Finally, the planning illustration shows how power assumptions depend on the effect a future study aims to detect. Smaller target effects require more participants per arm, under the stated assumptions. The illustration is not the original trial design plan and does not turn the current result into an estimate of observed power. This distinction helps separate study planning from interpretation of the completed endpoint comparison.

17. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record leaves several trial-specific questions unanswered. It describes the study as randomized but does not report how the allocation sequence was generated or concealed, or whether randomization was stratified. Masking is listed as none. The record does not provide baseline characteristics that would help assess group comparability.

The record’s phase information is internally unclear: the phase field is NA, the official title calls the study Phase II, and the arm descriptions use Phase 2 and Phase 3 labels. It also identifies SSRT as closed and includes a truncated phrase in the Phase 3 MTSRT description. The record does not explain the relationship between these descriptions or the timing and circumstances of the arm closure.

The primary response population consists of participants who completed a PSA evaluation at 21 months after treatment. The registry does not say how many participants lacked such an evaluation, how missing results were handled, or whether analyses were conducted in other populations. It also does not explain why the MTSRT endpoint group contains 20 participants while its safety group contains 22.

The comparison is reported as unadjusted, but the test and confidence-interval method are not identified. The original sample-size justification, prespecified analysis plan, multiplicity approach, interim analyses, and adjustment strategy are not reported in the registry record. Although several secondary outcomes are listed, their results and analyses are not posted. These gaps limit independent assessment of the full trial analysis and of outcomes beyond the primary PSA response measure.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: MRI-Mapped Dose-Escalated Salvage Radiotherapy Post-Prostatectomy: The MAPS Trial — NCT01411345.
• Registry record last updated 2026-05-05; status last verified 2026-03.
• Results first posted 2025-04-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

21. Record Summary

The MAPS record describes a randomized, parallel-arm salvage radiotherapy trial after prostatectomy, sponsored by University of Miami. Enrollment is 37, masking is listed as none, and trial status is active, not recruiting. The record identifies SSRT and MRI-mapped MTSRT, with the SSRT arm described as closed.

The primary endpoint is the percentage of participants with PSA less than 0.1 ng/mL at 21 months after study treatment. The posted rates are 66.6% for SSRT and 85.0% for MTSRT. The risk-difference estimate is 0.183, with a 95% confidence interval from -0.102 to 0.469 and an unadjusted p-value of 0.201. The interval includes zero, and the estimate remains uncertain.

The record lists secondary outcomes involving safety, quality of life, treatment failure, survival, and biomarkers, but their results are not reported in the registry record. Analysis details, missing-data procedures, and the trial’s original sample-size justification are also not reported.